15-65102117-G-C

Variant names:

• chr15-65102117-G-C
• rs1438801740
• NM_001163692.2:c.688C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001163692.2(UBAP1L):​c.688C>G​(p.Pro230Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,205,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P230S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: UBAP1L NM_001163692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96
• Publications: 0 publications found

Genes affected

UBAP1L (HGNC:40028): (ubiquitin associated protein 1 like) Predicted to enable ubiquitin binding activity. Predicted to be involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Predicted to be part of ESCRT I complex. [provided by Alliance of Genome Resources, Apr 2022]

UBAP1L Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
• retinal degeneration

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26022148).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163692.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP1L	NM_001163692.2	MANE Select	c.688C>G	p.Pro230Ala	missense	Exon 3 of 6	NP_001157164.1	F5GYI3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP1L	ENST00000559089.6	TSL:1 MANE Select	c.688C>G	p.Pro230Ala	missense	Exon 3 of 6	ENSP00000454012.1	F5GYI3
	UBAP1L	ENST00000907325.1		c.688C>G	p.Pro230Ala	missense	Exon 2 of 5	ENSP00000577384.1
	UBAP1L	ENST00000558802.1	TSL:5	n.240+448C>G		intron	N/A	ENSP00000452794.1	H0YKG2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152068 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000112 AC: 118 AN: 1053056 Hom.: 0 Cov.: 26 AF XY: 0.000109 AC XY: 54 AN XY: 497534

African (AFR) AF: 0.0000459 AC: 1 AN: 21766

American (AMR) AF: 0.00 AC: 0 AN: 7688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13118

East Asian (EAS) AF: 0.00 AC: 0 AN: 24674

South Asian (SAS) AF: 0.00 AC: 0 AN: 19328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2768

European-Non Finnish (NFE) AF: 0.000129 AC: 116 AN: 901098

Other (OTH) AF: 0.0000239 AC: 1 AN: 41808

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152068 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74270

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67960

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.17
Sift	Benign	0.12	T
Sift4G	Uncertain	0.057	T
Polyphen		1.0	D
Vest4		0.25
MutPred		0.18		Loss of sheet (P = 0.0104)
MVP		0.040
ClinPred		0.95	D
GERP RS		4.1
Varity_R		0.15
gMVP		0.39
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1438801740; hg19: chr15-65394455;